Early derivatives of polyimides such as polysuccinimides involved the straight forward ring opening and amide substitution of the carboxyl groups. Typically, primary or secondary amines were employed to amidate the carboxyl groups. Depending upon the degree of substitution and other reactive groups in the amine reactant, hydrophilic or hydrophobic compounds were made. A typical example of this is found in U.S. Pat. No. 3,846,380 to Fujimoto et al. In this patent the polysuccinimide is reacted with appropriate amines containing various functional groups followed by hydrolysis to open the succinimide rings not otherwise reacted with the amine reactant. The resulting polymer contained a wide range of properties useful as surface active agents. By selecting the kind and amount of the long chain amine used to form the resulting polymer, various physical and chemical properties could be readily obtained.
Amines have been known to react with the carboxyl group of polyaspartic acid or the anhyride, polyanhydroaspartic acid, as shown in French patent applications FR 78 12516 and 77 27769 to Jacquet et al. The amidation of some of the reactive sites of the imide or anhydride can be followed by one or more additional amines or hydrolyzed with a base. Such amides are suggested as being useful in cosmetic compositions such as hair shampoo, setting lotions, brushing lotions or dye depending upon the type and amount of amine employed in the amidation reaction. Most of these types of compounds are soluble in organic solvents such as alcohol.
Water soluble polyamides were investigated as possible drug carriers by Neuse, Perlwitz and Schmitt as reported in Die Angewandte Makromolekulare Chemie, 192 pp. 35-51 (1991). Twelve water soluble N-substituted polyaspartamides were synthesized form polysuccinimide by nucleophilic ring opening. The compounds contained solubilizing segments that comprise additional repeat units with drug-anchoring sites. Amine functions on side chains were obtained by using alkyl diamines such as 1,4 diamino heptane, 1-aminobutane, 1-amino octane, 1-(2-amino ethyl)piperazine, etc. The polymers had molecular weights in the range of from 6,000 to 8,000. More recently, polymeric micelles comprising block copolymers or polyethylene glycol and polyaspartic acid have been investigated as a possible drug carrier particularly in the treatment of tumors. The description of this investigation is found in Macromol. 1992, Invited Lect. IUPAC Int. Symp. Macromol., 34th (1993), Meeting date 1992, pp. 267-276, by K. Kataoka, et al.
It is known to cross-link polyaspartic acid and salts thereof by employing amines. An example of such compounds is found in U.S. Pat. No. 5,284,936 to Donachy et al. Such disclosure indicates that cross-linked polymers are prepared by the reaction of polyaspartic acid with an amino acids such as lysine, arganine, serine, tyrosine, etc. These compounds were found to be water insoluble and capable of absorbing water in amounts ranging from 20 to 90 times the weight of the dry polymer. In a related patent, U.S. Pat. No. 5,247,068, water insoluble cross-linked polypeptides are disclosed which are derived from lysine and glutamic acids in various mole percent ratios respectively.
As can be seen from the above noted publications, numerous different amines carrying various functional groups have been employed to produce polymers with different functions. Cross-linking of the polysuccinimide has been reported only with amino acids which are relatively expensive and limited as to useful end product.